Project Summary /Abstract (DIMC) The specialized expertise of the Diabetes Immune Monitoring Core (DIMC), a unit within Stanford's Human Immune Monitoring Center (HIMC), will provide SDRC investigators with the capacity to perform modern molecular, cellular and functional studies of human Immune cells in type 1 (T1D), type 2 (T2D) and type 3c (T3cD) diabetes. The SDRC's large group of collaborative investigators study a broad spectrum of Immunobiology in physiological or pathological settings, including transplant tolerance, inflammation, cell signaling, immune cell metabolism, immunogenic vs non-immunogenic cell death, genetics, epigenetics, islet immunology and immune therapy, among others. A central aspect of the DIMC is our direct focus on human immunology with the assessment of leukocytes in blood and tissues such as bone marrow, spleen, pancreatic islets and lymph nodes. An essential component supporting the SDRC studies is the provision of validated and standardized high dimensional instrumentation, reagents and assays to probe B, NK, T, myeloid and granulocytic cell lineages in blood and tissue from patients with or at-risk for diabetes. These robust tools in the DIMC has increased the number of SDRC investigators studying human diabetes at Stanford. The DIMC's current support of Stanford's organ transplantation tolerance program will also enhance our forthcoming human islet transplantation program for patients with T3cD and eventually T1D. The DIMC also provides training for investigators in specialized methods of human Immunology such as CyTOF, high dimensional flow cytometry (up to 40 parameter), cytokine/chemokine microbead arrays (Luminex), mixed lymphocyte reactions (MLR), T cell receptor (TcR) repertoire analysis via RNASeq and monitoring of B, T and APC responses to beta cells and their antigens. DIMC personnel will work closely with SDRC investigators to build efficient experimental strategies tailored to their needs. This support will help investigators develop the new clinical islet programs at the hospitals and clinics of Stanford Health Care. The DIMC will work closely with other research cores in the Stanford DRC. Together with the Clinical & Translational Core (CTC), Islet Procurement and Research Core (IPRC) and the Diabetes Genomics & Analysis Core (DGAC), the DIMC will integrate efforts permitting cellular, genetic, molecular, physiological and genome studies of human pancreas- and islet- associated cells relevant to diabetes, including immune, stromal and vascular cells. The DIMC also serves the Stanford DRC community by continuously developing new experimental capacity to match the explosion in sophisticated technologies. This includes assays to detect islet infiltrating immune cells, such as multi-ion beam imaging (MIBI). In summary, the DIMC will respond to the clear mandate of our SDRC community to providing cutting-edge immune monitoring resources, as well as providing investigators with technologies, reagents and assays along with pancreas- and islet-specific expertise and training to enable and expand their diabetes-related research at Stanford.